2024-01-20 07:45:19
Maintaining stable levels of oxidative stress is essential for cellular health, although this balance is usually deregulated in tumor cells. This imbalance makes tumor cells more sensitive to external changes that can increase stress in a way that is incompatible with cell survival. For this reason, numerous research explores oxidative stress-inducing therapies as a cancer treatment, and the field of nanomedicine offers promising advances.
A new work by researchers from the Higher Council for Scientific Research (CSIC) in Spain, identifies oxide nanoparticle coatings that specifically affect the growth of tumor cells by generating high levels of oxidative stress that end up negatively affecting their mitochondrial metabolism, which opens the possibility of its combined use in already established therapies.
Iron oxide nanoparticles are a novel tool in biomedicine: their small size and our body’s ability to metabolize them with very low toxicity make them suitable for non-invasive methods for the diagnosis and treatment of diseases such as cancer, where they are already They had been used for the selective transport of drugs.
“Now we have seen that the nanoparticles themselves and the molecules with which they are coated for biomedical use can have antitumor effects. These nanoparticles are like ‘solid nano-chancelles’”, explains Domingo F. Barber, a CSIC researcher at the National Center for Biotechnology (CNB) of the CSIC who has led the work. “They have a compact core of iron oxide that must be coated with different materials to provide more stability and less toxicity. “Our group has been analyzing different types of coating for years and seeing how they affect its entry into the cell, its accumulation and its degradation within it, but until now we had not studied its effect on cellular metabolism at a global level.”
The researcher points out: “We also knew that nanoparticles can increase cellular oxidative stress without significantly affecting the balance at certain doses. “Now we wonder if some type of coating could further enhance stress in tumor cells, where homeostasis is already deregulated, to levels that selectively lead to cell death.”
Neus Daviu, also a CNB researcher, details the analysis carried out: “We have used three different types of coatings on the nanoparticles and tested whether they affect cellular metabolism both in model cell lines of different types of tumor (breast, pancreas and glioma) and in “non-tumor lines of macrophages and endothelial cells that can also be found in tumors.”
The parameters studied are several. On the one hand, the metabolic activity of the cell, analyzing the functioning of the mitochondria, the organelle in charge of respiration. Not only do they change their shape, a clear symptom of malfunction, but they produce less ATP (the essential molecule for producing energy) and degrade more, since the cell detects that it is malfunctioning and eliminates them in a process called autophagy. Furthermore, Daviu points out, “there is a stop in the cell cycle: the tumor cells treated with the nanoparticles covered with DMSA (dimercaptosuccinic acid) grow much less, they remain as if stuck, a highly desired effect to stop the proliferation of tumors. ”
A tumor cell where changes in the morphology of the mitochondria can be seen (in green) after treatment with iron oxide nanoparticles coated with DMSA. (Photo: Neus Daviu / CNB / CSIC)
The researchers highlight the differential effect on the different tumor cell types used, with those of breast origin being the most sensitive to the effect of these nanoparticles. Although these data have been obtained in cell lines, other works by the same authors point to better functioning in vivo (in mice) of the antitumor therapy when administered through nanoparticles coated with DMSA, which highlights its potential for transport. targeting of drugs and their collaboration in the reduction of tumors.
The study is titled “DMSA-coated IONPs trigger oxidative stress, mitochondrial metabolic reprogramming and changes in mitochondrial disposition, hindering cell cycle progression of cancer cells.” And it is published in the academic journal Biomaterials. (Source: CNB/CSIC)
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